Mycobacterium tuberculosis: Ca. 30 % of humankind are infected with this pathogen, 10 % sicken from manifested tuberculosis. The special feature of these bacteria is that they are very acid-fast, they grow very slowly, and can survive in macrophages. This way, they are a great challenge in terms of therapy and prevention for physicians and scientists. The following article distinctly presents you all the relevant facts for exams concerning tuberculosis which are needed for the second state examination and clinical practice.

00:00
So isoniazid is probably
the first drug you need to know.
00:05
It's very similar to pyridoxine.
00:07
It inhibits cell wall
production in M.tuberclosis.
00:12
So the bacteria itself is not
able to make it cell wall.
00:15
Resistance develops and it's
rapidly developing if you're notusing with other medications.
00:21
It's often due to a point mutation one or two points,one of two points that code
for the critical enzymesresponsible for making
the cell wall.
00:30
It is not effective against
a lot of dominant organismshowever.
00:35
In terms of the toxicity,
the biggest thing that we areconcerned about is
neurotoxicity, which includesrestless leg, peripheral
neuritis and those thing wetreat with vitamin
B or pyridoxine.
00:47
Hepatotoxicity is
a concern as well.
00:50
You can develop abnormal
liver function tests.
00:53
You can develop jaundiceand you can develop hepatomegaly.
00:57
So it's important that you
monitor liver function testsregularly.
01:01
And you do a clinical exam
on these patients too.
01:04
One of the problems that we
have with isoniazid is that itinteractions with other
medications which includecarbamazepine,
phenytoin and warfarin.
01:14
So clearly this agent is working
through the cytochrome system.
01:18
One of the other issues that
we worry about is hemolysis inthose patients who have gluco
6 phosphotate deficiency.
01:25
So this is an important part
of your history before youprescribe this drug.
01:31
Another agent that we use
in TB treatment is rifampin.
01:35
So rifampin you became very
familiar it with when we weretalking about inducers
and inhibitors of cytochrome.
01:42
It's very bactericidal
side against mycobacteriumtuberculosis.
01:47
Now remember that the drug
itself is quite orange colored.
01:50
So it may discolor urine
and it may discolor the feces.
01:53
And sometimes the patients
come in and freaked outbecause as they are peeing
out orange.
01:57
Just reassure them that's
totally normal with this pill.
02:00
It's usually used
in combination.
02:02
Sometimes we use
it individually.
02:05
But quite frankly in the last
15 years I've never seenit used individually.
02:09
It's given as prophylaxis to
family members of TB patientson a fairly regular basis now.
02:16
In terms of how it works,
it inhibits DNA dependentRNA polymerase.
02:21
And rifampin is the prototypical
cytochrome inducersI mentioned before.
02:26
So you'll hear a lot about this
agent way out of proportionto it's level of use
in the community.
02:32
In terms of resistance to
rifampin, it is due to changesin drug binding of
this polymerase.
02:39
In terms of toxicity,
the toxicity is really lightchanged proteinuria, skin
rashes and thrombocytopenia.
02:46
You can also get nephritis
and hepatic dysfunction too.
02:50
Rifabutin is in the
same class as rifampin.
02:55
And it's equally
as effective as rifampin.
02:57
And it's actually preferred
in HIV positive patientsbecause it has fewer cytochrome
inducer effects.
03:04
Rifamixin is also another
agent in the same drug class.
03:08
And we've used this in
traveler's diarrheain the past.
03:12
Let's move on to
ethambutol or ETB.
03:15
It is an inhibitor of
arabinosyltranferases.
03:19
Now this particular protein is
a component of cell walls.
03:26
It is well absorbed and it
is excreted in the urine.
03:29
And it is always given
in combination with otherantituberculosis agents.
03:34
The toxicity of ethambutol
is usually reserved to visualdisturbances.
03:40
So patients interestingly enough
complain red or greencolor blindness.
03:44
They may also develop an optic
neuritis or retinal damage.
03:47
So a very close evaluation
of their ocular system,their visual system is really
important.
03:53
Sometimes patients may also
develop headache and they canalso develop confusion
and hyperuricemia.
04:00
One of the other rare
complications of thismedication is
peripheral neuritis.
04:05
Pyrazinamide is always given in combination with other drugs.
04:10
It's well absorbed.
04:11
It's excreted in the urine.
04:13
And it's half life is increase
in the liver or renal failure.
04:16
Pyrazinamide has non-gouty
polyarthalgia and that's reallycommon up to 40% of
patients develop this.
04:24
They also often will get
asymptomatic hyperucemia,myalgias, rash and
hepatic dysfunction.
04:31
Remember that you want to
avoid this agent in pregnancy.
04:34
Streptomycin is aminoglycoside,
I eluded to it earlier.
04:39
It's used in resistance
strains of tuberculosis.
04:43
And it's main concern like all
aminoglycosides isrenal toxicity
or renal dysfunction.
04:49
And of course we mentioned
before that aminoglycosides areinvolved with otosclerosis
and ototoxicity including someauditory as in not being
able to hear toxicity.
05:02
Amikacin is used in drug
resistant TB infections.
05:08
We also use ciprofloxacin
and ofloxacin drug resistant TB.
05:14
And we can use in combination
with the other TB drugs.
05:20
Ethionamide is a drug that
is very similar to isoniazid.
05:24
It's used in patients who have
isoniazid resistantstrains of TB.
05:29
Now paraaminosalicyclic acid or
PAS is also used but rarely nowbecause the resistance
is common.
05:39
It's relatively toxic agent
causes lot of GI irritationand peptic ulceration.
05:44
You don't need to know
this for your exam.
05:46
But in case you ever come across
this, you just know that is oneof these agents that we use a
lot but not so much anymore.

About the Lecture

The lecture Antituberculosis Drugs – Antimycobacterial Agents by Pravin Shukle, MD is from the course Antimicrobial Pharmacology. It contains the following chapters:

Tubercolosis Agents - First Line Drugs

Tubercolosis Agents - Second Line Drugs

Included Quiz Questions

A patient being treated for tuberculosis develops restless leg syndrome. Which of the following CORRECTLY describes the management of this scenario?

Start pyridoxine and continue isoniazid.

Discontinue isoniazid immediately, but maintain the other drugs in the regimen.

Observe the patient only, as it is usually a self-limiting side effect.

Switch to the 2nd line regimen of antituberculosis drugs.

Start probenecid and decrease dose of isoniazid.

Which antituberculosis drug works by inhibiting the DNA-dependent RNA polymerase?

Rifampin

Isoniazid

Streptomycin

Pyrazinamide

Ethambutol

Why is Rifabutin preferred over Rifampin for the management of tuberculosis in HIV+ patients?

Rifabutin has less cytochrome induction activity.

Rifabutin also has activity against the HIV virus.

Rifabutin is metabolized in the liver while rifampin is metabolized in the kidney.

Rifampin has a higher risk for renal failure compared to rifabutin.

The HIV virus produces esterases which break down rifampin but not rifabutin.

Which of the following may be found in up-to 40% of patients taking pyrazinamide?

Non-gouty polyarthralgia

Gout

Visual disturbances

Orange discoloration of urine and feces

Myalgia

Which drug is given on its own as prophylaxis to family members of patients with tuberculosis?

Rifampin

Ethambutol

Clarithromycin

Streptomycin

Isoniazid

Author of lecture Antituberculosis Drugs – Antimycobacterial Agents

Pravin Shukle, MD

Customer reviews

(1)
5,0 of 5 stars

5 Stars

5

4 Stars

0

3 Stars

0

2 Stars

0

1 Star

0

User Reviews

(1)
5,0 of 5 stars

5 Stars

5

4 Stars

0

3 Stars

0

2 Stars

0

1 Star

0

Subscribe to bookmark your content

Bookmarks will help you organize our more than 2000 medical videos,
and customize your learning experience for more efficiency and better results.

USMLE™ is a joint program of the Federation of State Medical Boards
(FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered
trademark of the Association of American Medical Colleges (AAMC).
None of the trademark holders are endorsed by nor affiliated with Lecturio.